Sturgeon B E, Sipe H J, Barr D P, Corbett J T, Martinez J G, Mason R P
Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
J Biol Chem. 1998 Nov 13;273(46):30116-21. doi: 10.1074/jbc.273.46.30116.
Cellular systems contain as much as millimolar concentrations of both ascorbate and GSH, although the GSH concentration is often 10-fold that of ascorbate. It has been proposed that GSH and superoxide dismutase (SOD) act in a concerted effort to eliminate biologically generated radicals. The tyrosyl radical (Tyr.) generated by horseradish peroxidase in the presence of hydrogen peroxide can react with GSH to form the glutathione thiyl radical (GS.). GS. can react with the glutathione anion (GS-) to form the disulfide radical anion (GSSG-). This highly reactive disulfide radical anion will reduce molecular oxygen, forming superoxide and glutathione disulfide (GSSG). In a concerted effort, SOD will catalyze the dismutation of superoxide, resulting in the elimination of the radical. The physiological relevance of this GSH/SOD concerted effort is questionable. In a tyrosyl radical-generating system containing ascorbate (100 microM) and GSH (8 mM), the ascorbate nearly eliminated oxygen consumption and diminished GS. formation. In the presence of ascorbate, the tyrosyl radical will oxidize ascorbate to form the ascorbate radical. When measuring the ascorbate radical directly using fast-flow electron spin resonance, only minor changes in the ascorbate radical electron spin resonance signal intensity occurred in the presence of GSH. These results indicate that in the presence of physiological concentrations of ascorbate and GSH, GSH is not involved in the detoxification pathway of oxidizing free radicals formed by peroxidases.
细胞系统中抗坏血酸和谷胱甘肽（GSH）的浓度高达毫摩尔级，尽管GSH的浓度通常是抗坏血酸的10倍。有人提出，GSH和超氧化物歧化酶（SOD）共同作用以消除生物产生的自由基。辣根过氧化物酶在过氧化氢存在下产生的酪氨酸自由基（Tyr.）可与GSH反应形成谷胱甘肽硫自由基（GS.）。GS.可与谷胱甘肽阴离子（GS-）反应形成二硫自由基阴离子（GSSG-）。这种高反应性的二硫自由基阴离子会还原分子氧，形成超氧化物和谷胱甘肽二硫化物（GSSG）。同时，SOD会催化超氧化物的歧化反应，从而消除自由基。这种GSH/SOD协同作用的生理相关性值得怀疑。在含有抗坏血酸（100 microM）和GSH（8 mM）的酪氨酸自由基生成系统中，抗坏血酸几乎消除了氧气消耗并减少了GS.的形成。在抗坏血酸存在的情况下，酪氨酸自由基会将抗坏血酸氧化形成抗坏血酸自由基。当使用快速流动电子自旋共振直接测量抗坏血酸自由基时，在GSH存在的情况下，抗坏血酸自由基电子自旋共振信号强度仅发生了微小变化。这些结果表明，在生理浓度的抗坏血酸和GSH存在时，GSH不参与过氧化物酶形成的氧化自由基的解毒途径。
